The results of the Nutritional Prevention of Cancer Trial (NPC) substantially impacted the evidence supporting selenium as a chemopreventive agent. These results, published in 1996, have been cited in the medical literature over 400 times in the last five years and have received considerable public attention. The original trial randomized 1312 subjects, all non-melanoma skin cancer (NMSC) patients, to 200 mcg/day of selenium or a matching placebo. In a second trial, 424 subjects, also NMSC patients were randomized to 400 mcg/day of selenium or placebo. Although the NPC study did not support a protective effect of selenium on the recurrence of NMSC, a 200mcg/day supplement of selenium in Baker's yeast significantly decreased total cancer mortality and incidence, as well as the incidence of cancers of the lung, colon and prostate. A preliminary analysis of the 400 mcg/day dose showed no significant difference in cancer incidence between the two treatment groups. After the publication of these startling results, the blinded phase of the trial ended and all subjects were offered the opportunity to take 200 mcg/day selenium supplements (Open-Label Phase). The Open-Label Phase has actively followed approximately 937 (54%) of the original participants from both trials since 1996. Approximately 553 (32%) chose to take the supplied selenium supplements. Every 6 months, all participants are assessed for incident cancers and other significant illnesses, signs and symptoms of selenium toxicity, and vital status. To date, 714 (41%) are deceased and 13 (0.7%) are lost to follow-up. The large and detailed database generated from the NPC trial, which has been routinely updated, is supplemented with more than 40,000 archived plasma samples collected throughout the trial. This proposal requests a final funding period for the NPC Trial and outlines three main goals of the next 3 years. These goals include: 1 ) based on the Data Safety Monitoring Board (DSMB) recommendations, to end the Open-Label Phase and stop active follow-up through a planned sequence of mailings and contacts; 2) to complete the documentation of reported illnesses and procedures and the vital status of all original participants in the two trials; and 3) to complete the reanalysis of the major endpoints, including major cancers and cardiovascular diseases.The Principal Investigator, Dr. James Marshall will be relocating to Roswell Park Cancer Institute (RPCI) as of July 2002. He will make frequent visits to Tucson to continue active oversight of the completion of this important project. To maintain oversight continuity, Dr. Mary Reid will serve as the Arizona-based PI. Utilizing her past experience as project director of NPC and research role as Research Director, she will continue to supervise the project staff, direct the management and analysis of the data, and work with Dr. Marshall and Dr. Anna Lillico to plan for manuscript preparation and publication. The project staff will otherwise remain the same, ensuring the efficiency and high quality data management that has characterized this trial. The proposed project will complete the data collection for the NPC trial and will utilize this invaluable resource to verify the effects of selenium supplementation through a series of publications.